This proposal aims to reveal basic principles underlying olfactory system function, organization, and development. The experimental plan takes advantage of the fruit fly Drosophila as a model system, which allows powerful genetic analysis and convenient physiological measurement of individual olfactory receptor neurons. The project seeks to define and characterize the diversity of olfactory receptor neurons that underlie odor coding in Drosophila, and to understand the molecular mechanisms that generate this diversity during development. A systematic analysis of the receptor neurons of the antenna will be continued in order to define the cellular basis of odor coding. The odor-response spectra and response dynamics of these neurons will be characterized in detail. The acj6 POU domain transcription factor will be analyzed to determine the molecular mechanisms by which it acts in establishing receptor neuron identity. Special attention will be accorded to its role in the regulation of odor receptor gene expression. Little is known about the means by which individual olfactory receptor neurons select, from among a large repertoire, which receptor genes to express. This project aims to identify components, both cis-acting and trans-acting, that are required for the process of receptor gene choice. One goal is to test the hypothesis that receptor gene choice is made in part through a combinatorial code of POU and LIM domain transcription factors. Hundreds of millions of people are afflicted by diseases carried by insects, many of which recognize and locate their human hosts largely through olfactory cues. Advances in the understanding of insect olfaction could lead to new means of controlling these insect pests.